Direct-acting antivirals for chronic hepatitis C: risk of hypoglycaemia in patients with diabetes

Monitor glucose levels closely in patients with diabetes during direct-acting antiviral therapy for hepatitis C, particularly within the first 3 months of treatment, and modify diabetes medication or doses when necessary. Patients with diabetes may experience symptomatic hypoglycaemia if diabetic treatment is continued at the same dose due to potential for an enhanced hypoglycaemic effect.

Advice for healthcare professionals:

  • rapid reduction in hepatitis C viral load during direct-acting antiviral therapy for hepatitis C may lead to improvements in glucose metabolism in patients with diabetes, potentially resulting in symptomatic hypoglycaemia if diabetic treatment is continued at the same dose
  • be vigilant for changes in glucose tolerance and advise patients of the risk of hypoglycaemia during direct-acting antiviral therapy, particularly within the first 3 months when the viral load is being reduced, and modify diabetic medication or doses when necessary
  • physicians who initiate direct-acting antiviral therapy in patients with diabetes should inform the healthcare professional in charge of the diabetic care of the patient
  • report any suspected adverse drug reactions associated with direct-acting antiviral therapies to the Yellow Card Scheme without delay

Evidence for hypoglycaemia during direct-acting antiviral therapy

Studies1 2 3 4 5 6 7 show that some patients with diabetes initiating direct-acting antiviral therapy for hepatitis C have experienced hypoglycaemia. The studies indicate that achieving sustained virological response (SVR) is associated with improvements in glycaemic control, compared to patients who relapse or are non-responders. Many studies recorded these changes in glycaemic control in the first 3 months of treatment. Some studies reported the need to adjust patient’s diabetic medication following changes in glucose metabolism, with up to 30% of patients requiring adjustments to their treatment.

An EU review confirmed the risk of hypoglycaemia in patients with diabetes who had been initiated on direct-acting antivirals for chronic hepatitis C. Information on the risk is being added to the Summary of Product Characteristics and Patient Information Leaflet for these medicines.

Patients with diabetes should be closely monitored for changes in glucose levels, particularly in the first 3 months of treatment, and adjustments to their diabetic medication or doses made where necessary.

Background

Direct-acting antivirals for chronic hepatitis C infection include: daclatasvir (Daklinza▼); sofosbuvir/velpatasvir (Epclusa▼); ledipasvir/sofosbuvir (Harvoni▼); sofosbuvir (Sovaldi▼); sofosbuvir/velpatasvir/voxilaprevir (Vosevi▼); dasabuvir (Exviera▼); ombitasvir/paritaprevir/ritonavir (Viekirax▼); glecaprevir/pibrentasvir (Maviret▼); and elbasvir/grazoprevir (Zepatier▼).

Report any suspected adverse drug reactions

Any suspected adverse drug reactions to direct-acting antivirals should be reported to us on a Yellow Card. Healthcare professionals, patients, and caregivers can report suspected side effects via the Yellow Card website or via the Yellow Card app. Download the app today via iTunes Yellow Card for iOS devices or via PlayStore Yellow Card for Android devices.

You can also use the app to access the latest safety information from MHRA about medicines and medical devices on the Newsfeed. Search for medicines to see details of Yellow Card reports others have made. Medicines of interest can also be added to a Watch List to receive news and alerts about new side effects and safety advice as it emerges.

Further information

Pharmacovigilance Risk Assessment Committee recommendations on signals adopted at the 1-4 October 2018 meeting.

Article citation: Drug Safety Update volume 12, issue 5: December 2018: 4.

  1. Ciancio A, et al. Significant improvement of glycemic control in diabetic patients with HCV infection responding to direct-acting antiviral agents. J Med Virol 2018; 90: 320–27. 

  2. Hum J, et al. Improvement in Glycemic Control of Type 2 Diabetes After Successful Treatment of Hepatitis C Virus. Diabetes Care 2017; 40: 1173–80. 

  3. Pavone P, et al. Improving of Glycaemic Control Associated with DAAs HCV Treatment Persists at SVR12. HIV Drug Therapy conference; Glasgow, UK; 28–31 October 2016. Poster P273. 

  4. Dawood AA, et al. Factors Associated with Improved Glycemic Control by Direct-Acting Antiviral Agent Treatment in Egyptian Type 2 Diabetes Mellitus Patients with Chronic Hepatitis C Genotype 4. Diabetes Metab J 2017; 41: 316–31. 

  5. Lyman A, et al. The Impact of Achieving Virologic Response from Hepatitis C Direct-Acting Antivirals on Diabetes Control. 2016 Fall Meeting of the Ohio College of Clinical Pharmacy (OCCP). Cleveland, OH, USA; 18 November 2016. Abstract 53. 

  6. Benitez-Gutierrez LM, et al. Rapid drop in serum glucose and hypoglycemia in chronic hepatitis C patients with diabetes during oral HCV therapy. AASLD 2016: The Liver Meeting; San Francisco, CA, USA; 13–17 November 2015. Abstract 1180. 

  7. LeClerc SB, et al. Viral response to hepatitis C direct-acting antivirals significantly improves diabetes control. AASLD 2016: The Liver Conference; Boston, MA, USA; 11–15 November 2016. Abstract 964. 

Published 18 December 2018